Remission In Systemic Lupus Erythematosus Research Articles

Evaluation of Lupus Low Disease Activity: Characteristics, Predictors, and Association with Disease Damage: A Retrospective Cohort from Two Tertiary Centers in Egypt

Abstract Background: Remission in systemic lupus erythematosus (SLE) is seldom achieved; making Lupus Low Disease Activity (LLDA) an alternative yet promising target. Aim of Study: The aim of this study was to evaluate the prevalence of remission and LLDA achieved, and the charac-teristics and predictors of LLDA, and its potential association with disease damage. Patients and Methods: The medical records of 243 patients fulfilling the 2012 Systemic Lupus Collaborating Clinics (SLICC) classification criteria for SLE and managed at Cairo and Ainshams Universities from January to December 2019 were viewed. Remission was categorized to: (i) Complete remission off glucocorticoid (GC) and Systemic Lupus Ery-thematosus Disease Activity Index-2K (SLEDAI-2K) = zero (antimalarial only); (ii) Clinical remission off GC with sero-logic activity (SKLEDAI-2K £4); (iii) Clinical remission on GC £5mg/day (SLEDAI-2K score £ 4 and serologic activity). LLDA was defined as SLEDAI-2K £4 in the absence of major organ involvement, GC dosage £7.5mg/day. Disease damage was assessed through the Systemic Lupus International Col-laborating Clinics/American College of Rheumatology Damage Index (SDI). Results: Seventy two (29.6%) patients achieved LLDA at the last visit; whereas 142 (58.4%) patients had a SLEDAI-2K score >4 and/or received a GC dosage of >7.5mg. One (0.4%) and 28 (11.5%) patients achieved clinical remission off and on GC, respectively. None of the patients achieved complete clinical and serologic complete remission. Patients achieving LLDA had an older age of onset compared to those with higher disease activity (p=0.003), and a lower prevalence of fever (p=0.009), weight loss (p=0.07), cutaneous vasculitis (p=0.002), serositis (p=0.006), nephritis (p=0.02), a lower median SDI score, and lower prevalence of developing severe damage (SDI ³3) (p=0.04). Predictors of LLDA were an older age of onset [p=0.006 (OR=1.05; 95% CI=1.01-1.09)] and weight loss [p=0.009 (OR=5; 95% CI=1.9-16.5)]; whereas patients with LLDA were less likely to have cutaneous vas-culitis [p=0.01 (OR=0.2; 95% CI=0.06-0.7)] or pleurisy and/or pleural effusion [p=0.001 (OR=0.2; 95% CI=0.1-0.5)].Conclusion: Achieving remission was substantially low. Lupus Low Disease Activity (29.6%) was associated with a higher age of onset, several distinct clinical characteristics, and lower damage.

Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort

ObjectivesRemission in systemic lupus erythematosus (SLE) is defined through a combination of ‘clinical SLE Disease Activity Index (cSLEDAI)=0’, ‘physician's global assessment (PGA) <0.5’ and ‘prednisone (PDN) ≤5 mg/day’. We investigated...

Treat to target in systemic lupus erythematosus

For the first time, the European League Against Rheumatism (EULAR) recommendations for the management of systemic lupus erythematosus (SLE) include atreat to target (T2T) strategy, naming remission as the main target. The aim is to improve the long-term survival, prevent damage and optimize the health-related quality of life. Compared to rheumatoid arthritis (RA) for which the T2T approach is already widely used, establishing T2T in SLE remains challenging due to its heterogeneity and limited treatment options. The aim of this article is to outline the current status of the T2T concept for SLE and to identify challenges and particularities. A special focus is placed on the use of activity scores and the importance of steroids in targeted treatment of SLE. The use of T2T for SLE remains achallenge. With the definitions of the lupus low disease activity states (LLDAS) and the definitions of remission in SLE (DORIS) abig step forward has been taken on the road towards the ideal treatment target; however, many aspects of the "treat" remain unclear. As an example, due to alack of data there are no explicit strategies for steroid reduction although it is often mandatory to achieve the targets. The T2T also includes much more than only immunosuppressive treatment and antimalarial agents, as disease damage which has already occurred and damage due to drugs, concomitant phenomena (such as depression) and comorbidities as well as measures for secondary prophylaxis must also be included.

Relationship between remission, disease activity and patient-reported outcome measures in patients with recent-onset systemic lupus erythematosus.

ObjectiveDefinitions of remission in systemic lupus erythematosus (SLE; DORIS (1A/1B/2A/2B)), disease activity assessments and patient-reported outcome measures (PROMs) are useful in shared decision making between patients with SLE and physicians. We used longitudinal registry data from well-characterized Swedish patients with recent-onset SLE to explore potential correlations between DORIS status or disease activity, and PROMs.MethodsPatients from the Clinical Lupus Register in North-Eastern Gothia, Sweden, who fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics classification criteria without prior organ damage, were enrolled at diagnosis. Data on treatments, serology, remission status (DORIS), disease activity (SLE Disease Activity Index-2000 (SLEDAI-2K)) and PROMs (quality of life: EuroQoL-5 Dimensions (EQ-5D); pain intensity, fatigue and well-being: visual analog scale (VAS) 0–100 mm) were collected during rheumatology clinic visits at months 0 (diagnosis), 6, 12, 24, 36, 48 and 60. Correlations were assessed using Pearson correlation and/or beta regression coefficients.ResultsA total of 41 patients were enrolled (median age = 39 years, 80% female, 85% white). Achievement of DORIS 1A and 2A (neither of which includes serology) significantly correlated with all PROMs (EQ-5D: p ≤ 0.02; pain: p = 0.0001; fatigue: p = 0.0051; well-being: p < 0.0001). Disease activity measures were correlated with VAS pain intensity (p < 0.03) and VAS well-being (p < 0.04).ConclusionsOur findings illustrate the importance of the interplay between remission, disease activity assessments and PROMs. PROMs may be a useful tool in clinical practice, being administered prior to patient visits to streamline clinical care.

Defining remission in systemic lupus erythematosus: still elusive?

Defining remission in systemic lupus erythematosus: still elusive?

Definitions of remission in systemic lupus erythematosus: a post-hoc analysis of two randomised clinical trials.

The Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) international task force has proposed remission definitions that are amenable to scientific testing. In this study, we aimed to evaluate their suitability as outcome measures in studies of systemic lupus erythematosus. In this post-hoc study, we applied remission definitions as specified by DORIS criteria at multiple timepoints in the BLISS-52 (n=865) and BLISS-76 (n=819) clinical trials. All definitions required physician's global assessment scores less than 0·5 (possible range 0-3). The DORIS 1 definitions required clinical systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K)=0 (with serological items excluded). The DORIS 2 definitions required a score of D or E in all British Isles Lupus Assessment Group (BILAG) domains. The definitions were assessed in the trial populations both with (on therapy) and without (off therapy) treatment allowance-ie, low-dose glucocorticoids (prednisone ≤5 mg/day) and maintenance immunosuppressive and biological agents. Antimalarial agents were allowed in all definitions. The definitions were applied irrespective of serological activity (anti-double stranded DNA positivity, or low C3 or C4) and with normal serology. Finally, we applied modifications similar to DORIS on therapy but allowing higher prednisone doses (≤10 mg/day). In the pooled dataset, the remission definition most frequently attained was the modified (prednisone ≤10 mg/day) DORIS 1a on therapy definition, which required a SLEDAI-2K score of 0 and permitted serological activity (237 [17·8%] of 1333 participants at week 52), followed by the unmodified (predisone ≤5 mg/day) DORIS 1 on therapy definition (140 [10·5%] of 1336 participants at week 52) based on these two definitions. We detected no significant difference between the placebo and belimumab groups. Proportions of patients achieving off therapy and BILAG-based definitions were low (≤0·9% at all timepoints). Sustained attainment of certain on therapy definitions showed an ability to discriminate between patients who received belimumab 10 mg/kg and patients who received placebo. Attainment of DORIS remission definitions was infrequent overall. Use of clinical SLEDAI-2K=0 in the definitions yielded higher proportions of attainment than did use of BILAG D or E. Attainment was also higher using definitions that allowed for serological activity and maintenance treatment. Addition of the durability aspect to on therapy definitions led to an ability to discriminate between belimumab and placebo. Swedish Rheumatism Association, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet Foundations.

Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study.

Validated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission. In this study, we aimed to assess the attainability and effect on disease outcomes of the DORIS definitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE. In this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares. Between May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent. Attainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions. UCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.

Glucocorticoid withdrawal in systemic lupus erythematosus: are remission and low disease activity reliable starting points for stopping treatment? A real-life experience

ObjectivesTo evaluate the proportion of patients who have successfully withdrawn glucocorticoids (GCs) in a longitudinal cohort of patients with systemic lupus erythematosus (SLE) over a period of 6 years; to...

Problems of low activity and remission in systemic lupus erythematosus

In recent years, the long-term survival of patients with systemic lupus erythematosus (SLE) has increased to more than 90%, but there are still quite a few unresolved problems. Although the main objective of the concept of «Treatment of SLE to target» is «remission of symptoms and absence of organ damage», it was recognized that there is currently no generally accepted definition of remission in SLE. The article discusses different variants of the definition of «remission» in SLE.

Risk factors for irreversible organ damages in peri- and postmenopausal women with systemic lupus erythematosus

Objective: to identify irreversible organ damages and factors influencing their development and to compare existing musculoskeletal injuries with the activity of systemic lupus erythematosus (SLE).Patients and methods. The investigation enrolled 197 peri- and postmenopausal female outpatients (mean age, 50.94±9.1 years) with SLE, who were followed up at Clinical Rheumatology Hospital Twenty-Five, Saint Petersburg. The mean disease duration was 9.7±7.5 years. Cytostatic and glucocorticoid (GC) treatment regimens and dosages in the examinees were analyzed on the basis of their primary medical records. The investigators assessed the current disease activity by the SLE Disease Activity Index (SLEDAI-2K) and the Lupus Low Disease Activity State (LLDAS) and irreversible organ damages by the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (DI).Results and discussion. 93.4% of the patients continued to receive GS therapy at the time of inclusion in the study. The median GS maintenance dose was 12.5 mg/day. Almost half of the patients (n=86/43.7%) were in menopause (its mean duration was 12.8±7.1 years). Half of the examinees were noted to have remission (n=36/18.3%) or low SLE activity (n=92/46.7%) according to the SLEDAI-2K. Fifty-seven (28.9%) patients met all 5 LLDAS criteria; at the same time other 96 (48.7%) patients met 4 out of the 5 criteria, the 5th criterion being a high GC maintenance dose. High DI scores of ≥4 were found in two thirds (n=131/66.5%) of the examinees. Musculoskeletal system injuries ranked first among other disorders: osteoporosis (OP) and muscle weakness were detected in 76 (38.6%) and 69 (35.0%) patients, respectively. Regression analysis involving all statistically significant factors showed that the degree of damage was influenced by age (p=0.013215), total GS dose (p=0.000047), and previous therapy with cyclophosphamide (p=0.041505).Conclusion. The contribution of GS therapy to irreversible damage accrual is obvious in peri- and postmenopausal women with SLE. Timely dose adjustment or complete withdrawal of GS during remission in SLE is one of the key factors that substantially reduce the risk of progression of irreversible organ damages due to the prevention of OP and osteoporotic fractures in these patients.

Factors associated with remission in patients with systemic lupus erythematosus: new insights into a desirable state.

The primary aim of this study was to assess demographic, clinical, and serological factors associated with remission in systemic lupus erythematosus (SLE). A retrospective cohort study was performed. We examined relevant features in patients with SLE with a follow-up of at least 8years from active disease (SLE Disease Activity Index-2000 [SLEDAI-2K] ≥6). The primary outcome was to assess various remission states in SLE according to disease activity and treatment. Differences between groups were assessed by Student's t test and chi-square test for continuous and categorical variables, respectively. Multivariate Cox proportional hazard analysis was used to assess association between variables, and we performed a Kaplan-Meier analysis with log rank test to evaluate time to remission. One hundred twenty-four patients fulfilled our inclusion criteria: 116 (93.54%) were women with a mean age of 30.23 ± 8.52years. Twenty-four patients (19.35%), 25 patients (20.16%), and 16 patients (12.9%) achieved complete remission, clinical remission on corticosteroids, and clinical remission off corticosteroids, respectively. SLEDAI-2K at 3rd month of follow-up (HR = 0.85, 95% CI = 0.73-0.98, p = 0.029) and total number of disease flares (HR = 0.73, 95% CI = 0.56-0.95, p = 0.024) were associated with complete remission, and total number of disease flares (HR = 0.80, 95% CI = 0.67-0.95, p = 0.011) was associated with clinical remission on corticosteroids. Our findings are clinically relevant to encourage an intensive immunosuppressive treatment and close monitoring early after active disease.

Clinicians approaches to management of background treatment in patients with SLE in clinical remission: results of an international observational survey

BackgroundThe definition of remission in systemic lupus erythematosus (SLE) remains unclear, especially how background treatment should be interpreted.ObjectiveTo determine preferences of clinicians in treatment of patients in clinical remission from...

Treat to target, remission and low disease activity in SLE.

Despite improvements in survival, outcomes of contemporary treatment of systemic lupus erythematosus (SLE) are unacceptable. Unlike in many diseases, treat-to-target (T2T) approaches have not been adopted in SLE, owing to a lack of validated targets to treat towards. Therefore, it is a key goal to validate target state definitions such as low disease activity and remission, and test their implementation in clinical practice and clinical trials. In this article, we review recent advances in T2T approaches in SLE, and emerging evidence-based consensus on definitions of remission and low disease activity that are needed to underpin such approaches. We conclude that, while more work is needed, much has been achieved and at least for low disease activity the lupus low disease activity state definition appears to have utility and validity for the study of SLE. Application to routine clinical care awaits validation of improved outcomes from T2T studies based on these targets.

A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)

ObjectivesTreat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to...

Remission in systemic lupus erythematosus: durable remission is rare

IntroductionRemission is the ultimate goal in systemic lupus erythematosus (SLE). In this study, we applied four definitions of remission agreed on by an international collaboration (Definitions of Remission in SLE,...

Understanding remission in real-world lupus patients across five European countries.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased mortality and significant personal, psychological and socioeconomic consequences. An agreed definition of remission is needed and lacking. We sought to visualize 'remission in SLE' in European patients considered by their physicians to be 'in remission' by comparing the reported symptom burden as reported by treating physicians for patients considered to be 'in remission' and those not considered to be 'in remission'. Data for 1227 patients drawn from a multinational, real-world survey of patients with SLE consulting practising rheumatologists and nephrologists in France, Germany, Italy, Spain, and the UK show that physicians classed their patients as 'in remission' despite a considerable ongoing symptom burden and intensive immunosuppressive medication. Patients considered to be 'in remission' still had a mean of 2.68 current symptoms vs 5.48 for those considered to be not 'in remission' (p < 0.0001). The most common symptoms among those seen to be 'in remission' were joint symptoms, fatigue, pain, mucocutaneous involvement, haematological manifestations and kidney abnormalities. The current analysis highlights important ongoing disease activity, symptom burden and immunosuppressive medication in European patients with SLE considered by their treating physician to be 'in remission'. For a further improvement of outcome, there is an urgent need for an international consensus on the definitions for remission among patients with SLE.

Prolonged Remission in SLE Revisited: An Old Wine in a New Bottle

To achieve sustained remission is the ultimate goal of any maintenance treatment used in systemic lupus erythematosus (SLE) — as well as the dream of any clinician in charge of patients with SLE. While in other autoimmune diseases, such as rheumatoid arthritis, it is easier to identify which patients achieved remission or low disease activity levels, the concept of remission is more difficult to define and harder to achieve in SLE, owing to the heterogeneity of this condition, the multiple organs affected, and the many activity scores used. In this issue of The Journal , Steiman, et al 1, from the University of Toronto Lupus Clinic, interestingly revisit the concept of sustained and prolonged remission in patients with SLE followed between 1970 and 2011 using a standardized protocol at clinic visits. The authors conducted a study focused on prolonged clinical remission (clinically quiescent), with or without serological activity, in a cohort including more than 1600 SLE patients with a very long followup (mean disease duration, 21 yrs). Of interest, only around 2% of patients achieved prolonged (at least 5 yrs) clinical remission, without any underlying immunosuppressive drug (except for antimalarials). An additional subset of patients who achieved remission while taking medical treatment are described. The authors used very strict definition criteria for serologically and clinically quiescent disease: at least a 5-year period without evidence of clinical activity [SLE Disease Activity Index 2000 (SLEDAI-2K) = 0]. Clinically quiescent but serologically active disease allowed SLEDAI-2K scores ≤ 4, positive anti-dsDNA antibody and/or hypocomplementemia only. Patients with prolonged remission had a lower burden of disease activity and disease damage. Further, the authors made an attempt to identify predictors of prolonged remission. Interestingly, regression models revealed that patients with late disease onset and those with less skin disease were more likely to achieve … Address correspondence to Dr. Gomez-Puerta, Division of Rheumatology, Immunology and Allergy, PBB-B3; Section of Clinical Sciences, Brigham and Women’s Hospital, 221 Longwood Ave., 3rd floor, Boston, Massachusetts 02115, USA. E-mail: jgomezpuerta{at}mail.harvard.edu

Impact of Environmental Factors on Efficacy of Glucocorticoids in Chinese Population with Systemic Lupus Erythematosus

Although glucocorticoids (GCs) are effective in inducing remission in systemic lupus erythematosus (SLE) patients, there is a significant variation in response to therapeutic GCs, and some patients do not achieve full remission. The aim of this study was to explore the impact of environmental factors on the efficacy of GCs in a Chinese population with SLE. This was a prospective cohort study, and a total of 260 SLE patients treated with GCs (prednisone) were followed up for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index. Environmental factors were collected using a questionnaire. Single-variable analysis and multivariate logistic regression analysis were used to discriminate the impact of environmental factors on the efficacy of GCs. Two hundred forty-seven patients (95.00 %) completed the 12-week follow-up. Among these patients, 131 (53.04 %) were classified into sensitive group and 116 (46.96 %) were classified into insensitive group. Results from logistic analysis showed that the following environmental factors were significantly associated with decreased efficacy of GCs: high salt intake (OR = 3.464, 95%CI = 1.481-8.102, P = 0.004), introverted personality (OR = 3.550, 95%CI = 1.901-6.628, P < 0.0001), experience with negative life events (OR = 5.526, 95%CI = 1.612-18.946, P = 0.007), and history of allergy (OR = 2.966, 95%CI = 1.312-6.704, P = 0.009). These results indicate that environmental factors, including salt intake, personality, experience with negative life events, and history of allergy, may play an important role in the efficacy of GCs in the Chinese population with SLE.

CD4+Foxp3+ regulatory T cells prolong drug-induced disease remission in (NZBxNZW) F1 lupus mice

IntroductionThe ability to ameliorate murine lupus renders regulatory T cells (Treg) a promising tool for the treatment of systemic lupus erythematosus (SLE). In consideration to the clinical translation of a Treg-based immunotherapy of SLE, we explored the potential of CD4+Foxp3+ Treg to maintain disease remission after induction of remission with an established cyclophosphamide (CTX) regimen in lupus-prone (NZBxNZW) F1 mice. As a prerequisite for this combined therapy, we also investigated the impact of CTX on the biology of endogenous Treg and conventional CD4+ T cells (Tcon).MethodsRemission of disease was induced in diseased (NZBxNZW) F1 mice with an established CTX regimen consisting of a single dose of glucocorticosteroids followed by five day course with daily injections of CTX. Five days after the last CTX injection, differing amounts of purified CD4+Foxp3+CD25+ Treg were adoptively transferred and clinical parameters, autoantibody titers, the survival and changes in peripheral blood lymphocyte subsets were determined at different time points during the study. The influence of CTX on the numbers, frequencies and proliferation of endogenous Treg and Tcon was analyzed in lymphoid organs by flow cytometry.ResultsApart from abrogating the proliferation of Tcon, we found that treatment with CTX induced also a significant inhibition of Treg proliferation and a decline in Treg numbers in lymphoid organs. Additional adoptive transfer of 1.5 × 106 purified Treg after the CTX regimen significantly increased the survival and prolonged the interval of remission by approximately five weeks compared to mice that received only the CTX regimen. The additional clinical amelioration was associated with an increase in the Treg frequency in the peripheral blood indicating a compensation of CTX-induced Treg deficiency by the Treg transfer.ConclusionsTreg were capable to prolong the interval of remission induced by conventional cytostatic drugs. This study provides valuable information and a first proof-of-concept for the feasibility of a Treg-based immunotherapy in the maintenance of disease remission in SLE.

Immunoinflammatory markers and disease activity in systemic lupus erythematosus: something old, something new

This study assessed the utility of some novel inflammatory markers compared with traditional laboratory markers in patients with systemic lupus erythematosus (SLE). In a cohort of 43 SLE patients (19 with inactive and 24 with active SLE) and 20 healthy controls, serial measures of soluble vascular cell adhesion molecule (sVCAM-1) were significantly associated with SLE disease activity, scored using the British Isles Lupus Assessment Group index. Inflammatory markers neopterin and soluble intercellular adhesion molecule (sICAM-1) appeared to be clinically useful for isolated assessments of disease activity. Both antibodies to double-stranded DNA (anti-dsDNA) and sVCAM-1 were relatively good markers of disease activity and could help to predict remission or monitorthe therapeutic response in SLE.